Biochemical, behavioral and electrophysiological evidence suggests that some of the clinical effects of neuroleptics (both antipsychotic properties and neurological side effects) and of d-amphetamine (stereotyped behavior and acute paranoid psychosis) are primarily mediated through their action on the dopamine system. Most of these studies examine, either directly or indirectly, the effects of these drugs on the dopamine cells themselves, rather than on the neurons which are innervated by the dopamine system. In addition, the great majority of evidence on the CNS effects of these drugs is derived from acute experiments in which the effects of a single dose are studied. However most of the important clinical effects of these drugs are seen only after days to months of continuous administration. The research proposed here is divided into two parts. The first part consists of studies investigating the acute effects of antipsychotic drugs on postsynaptic dopamine receptors in the various areas of the brain which are innervated by that system, including the frontal cortex, accumbens nucleus, and the caudate nucleus. The second part consists of chronic studies in which the effects of repeated administration of antipsychotic drugs and d-amphetamine on dopamine presynaptic and postsynaptic receptors will be determined. In these experiments single-unit-recording and microiontophoretic techniques will be used to determine both the acute and chronic changes induced in the activity of neurons which are innervated by the dopamine system, and in the activity of dopaminergic neurons themselves. The information emerging from these studies should further our knowledge of how and where d-amphetamine and the antipsychotic drugs act in the brain. It is hoped that such information will ultimately lead to a greater understanding of the possible mechanisms underlying psychosis, as well as to the development of neuroleptic agents with optimal antipsychotic properties and minimal neurological side effects.